Alzheimer's disease (AD) and Parkinson's disease (PD) are generally considered separate disease entities. However, there is extensive overlap among the clinical and pathologic features, indicating that common mechanisms contribute to neurodegeneration in these disorders. Our preliminary studies from both Emory and Iceland reveal a significantly increased crossed familial risk of AD and PD, suggesting that there are common genetic predispositions in "sporadic" late-onset cases of both diseases. Capitalizing on the ability to examine extended pedigrees in Iceland in collaboration with deCODE Genetics, our exciting preliminary findings demonstrate novel loci associated with both AD and PD., In the proposed collaborative studies between Emory and deCODE Genetics, we test our central hypothesis that a novel susceptibility gene on chromosome 7p contributes to both AD and PD risk in the Emory ADC subjects, and is more strongly associated with those cases with overlapping cognitive and extrapyramidal features. In specific aim 1, we test the association of candidate genes at the chromosome 7p locus with AD subjects in a case-control study using subjects in the Emory ADC. In specific aim 2, we test the association of candidate genes at the chromosome 7p locus with PD subjects in a case-control study using subjects in the Emory Parkinson's Disease Center. In specific aim 3, we propose to perform detailed genotype-phenotype correlations in the Emory AD and PD subjects to understand more precisely the role of the chromosome 7p locus in the clinical manifestations of AD and PD. Together, these aims will test our central hypothesis and advance our understanding of the complex genetics of AD, PD, and overlap syndromes.